The goal of the proposed experiments is to understand the role of cortical activity in the development of the corticospinal (CS) system in the cat. The cat CS system is immature at birth and continues to develop during early postnatal life. Neural activity during development appears to play a vital role in determining the topographic organization of the CS system and in establishing specific, functional connections between CS axons and their neuronal targets in the spinal cord. The proposed experiments will determine the topographic distribution of the neurotrophins BDNF and NT-3 during development, with respect to the critical period for CS development. In a second series of experiments, sensory-motor cortex will be silenced early in development. Then, either constraint-induced movement therapy or pyramidal tract stimulation will be implemented for four weeks. This aim will determine the efficacy of the rehabilitation regimens in guiding CS development toward a more normal pattern. Since abnormal CS development in humans often results in permanent disabilities, understanding the factors that cause abnormal CS development, and the efficacy of behavioral interventions in guiding the CS system toward a more normal development, is highly clinically significant. [unreadable] [unreadable]